Endoscopic or Surgical Myotomy in Patients with Idiopathic Achalasia.

BACKGROUND: Pneumatic dilation and laparoscopic Heller's myotomy (LHM) are established treatments for idiopathic achalasia. Peroral endoscopic myotomy (POEM) is a less invasive therapy with promising early study results. METHODS: In a multicenter, randomized trial, we compared POEM with LHM plus Dor's fundoplication in patients with symptomatic achalasia. The primary end point was clinical success, defined as an Eckardt symptom score of 3 or less (range, 0 to 12, with higher scores indicating more severe symptoms of achalasia) without the use of additional treatments, at the 2-year follow-up; a noninferiority margin of -12.5 percentage points was used in the primary analysis. Secondary end points included adverse events, esophageal function, Gastrointestinal Quality of Life Index score (range, 0 to 144, with higher scores indicating better function), and gastroesophageal reflux. RESULTS: A total of 221 patients were randomly assigned to undergo either POEM (112 patients) or LHM plus Dor's fundoplication (109 patients). Clinical success at the 2-year follow-up was observed in 83.0% of patients in the POEM group and 81.7% of patients in the LHM group (difference, 1.4 percentage points; 95% confidence interval [CI], -8.7 to 11.4; P = 0.007 for noninferiority). Serious adverse events occurred in 2.7% of patients in the POEM group and 7.3% of patients in the LHM group. Improvement in esophageal function from baseline to 24 months, as assessed by measurement of the integrated relaxation pressure of the lower esophageal sphincter, did not differ significantly between the treatment groups (difference, -0.75 mm Hg; 95% CI, -2.26 to 0.76), nor did improvement in the score on the Gastrointestinal Quality of Life Index (difference, 0.14 points; 95% CI, -4.01 to 4.28). At 3 months, 57% of patients in the POEM group and 20% of patients in the LHM group had reflux esophagitis, as assessed by endoscopy; at 24 months, the corresponding percentages were 44% and 29%. CONCLUSIONS: In this randomized trial, POEM was noninferior to LHM plus Dor's fundoplication in controlling symptoms of achalasia at 2 years. Gastroesophageal reflux was more common among patients who underwent POEM than among those who underwent LHM. (Funded by the European Clinical Research Infrastructure Network and others; ClinicalTrials.gov number, NCT01601678.).

Endoscopy versus radiology in post-procedural monitoring after peroral endoscopic myotomy (POEM).

BACKGROUND: The newly developed technique of peroral endoscopic myotomy (POEM) has been shown to be effective in several short- and mid-term studies. Limited information is available about the adequacy of immediate post-POEM monitoring tests. METHODS: POEM was performed under general anesthesia in 228 patients (59.6% male, mean age 45.6 ± 15.5 years). Post-procedural checks comprised clinical and laboratory examination, and, during post-procedure days 1-5, endoscopy and-in the first 114 cases-radiologic examination using water-soluble contrast (1st group); the remaining patients underwent post-procedure controls without radiology (2nd group). Main outcome was value of endoscopic compared to radiologic control for recognition of early adverse events. RESULTS: In the first group, routine fluoroscopic contrast swallow suggested minor leakages at the mucosal entry site in two cases which was confirmed endoscopically in only one. Endoscopy revealed two minor entry site leakages and, in six additional cases, dislocated clips without leakage (overall 5.3%). All eight patients underwent reclipping and healed without clinical sequelae. In the 2nd group, endoscopy showed 5 clip dislocations (all reclipped) and one ischemic cardiac perforation in a patient with clinical deterioration on post-POEM day 1 who had to undergo surgery after confirmation of leakage by CT. CONCLUSIONS: Radiologic monitoring (contrast swallow) after POEM is not useful and can be omitted. Even routine endoscopic monitoring for detection and closure of minor defects of the mucosal entry site yields limited information with regards to final outcome; major complications are very rare and probably associated with clinical deterioration. Clinical Trials Gov Registration number of the main study: NCT01405417.

Association between Weather-Related Factors and Cardiac Arrest of Presumed Cardiac Etiology: A Prospective Observational Study Based on Out-of-Hospital Care Data.

OBJECTIVE: The objective of this study was to determine the association between weather-related factors and out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology. METHODS: This was a prospective observational study performed in a prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany) and data from the local weather station were evaluated over a 5-year period. Weather data (temperature, humidity, air pressure, wind speed) were obtained every minute and matched with the associated rescue mission data. Lowess-Regression analysis was performed to assess the relationship between the above-mentioned weather-related factors and OHCA of presumed cardiac etiology. Additionally, varying measuring-ranges were defined for each weather-related factor in order to compare them with each other with regard to the probability of occurrence of OHCA. RESULTS: During the observation period 1,558 OHCA with presumed cardiac etiology were registered (age: 67 ± 19 yrs; 62% male; hospital admission: 37%; survival to hospital discharge: 6.7%). Compared to moderate temperatures (5 - 25°C), probability of OHCA-occurrence increased significantly at temperatures above 25°C (p = 0.028) and below 5°C p = 0.011). Regarding air humidity, probability of OHCA-occurrence increased below a threshold-value of 75% compared to values above this cut-off (p = 0.006). Decreased probability was seen at moderate atmospheric pressure (1000 hPa - 1020 hPa), whereas increased probability was seen above 1020 hPa (p = 0.023) and below 1000 hPa (p = 0.035). Probability of OHCA-occurrence increased continuously with increasing wind speed (p < 0.001). CONCLUSIONS: There are associations between several weather-related factors such as temperature, humidity, air pressure, and wind speed, and occurrence of OHCA of presumed cardiac etiology. Particularly dangerous seem to be cold weather, dry air and strong wind.

Early adverse events of per-oral endoscopic myotomy.

BACKGROUND AND AIMS: The recently developed technique of per-oral endoscopic myotomy (POEM) has been shown to be effective for the therapy of esophageal motility disorders. Limited information is available about POEM adverse events (AEs). METHODS: POEM was performed on 241 patients (58% male; mean age, 47.4 ± 16.4 years) under general anesthesia over 61 months. The main outcome was the rate of intra- and post-procedural AEs. Post-procedural checks comprised clinical and laboratory examinations and endoscopy, with further follow-ups performed at 3, 6, and 12 months. RESULTS: Of the 241 procedures, 238 were successfully completed (mean procedure time, 100.2 ± 39.5 min). Reasons for abortion were excessive submucosal fibrosis preventing submucosal tunneling. Three patients had severe procedural-related AEs (SAE rate, 1.2%); 1 case of pneumothorax required intra-procedural drainage, and 2 patients had delayed SAEs (1 ischemic gastric cardia perforation and 1 hemothorax, both leading to surgery). The overall rate of minor AEs was 31.1%, mainly prolonged intra-procedural bleeding (>15 min hemostasis) and defects of the mucosa overlying the tunnel; none led to clinically relevant signs or symptoms. Patients experiencing any AE had a significantly prolonged hospital stay (P = .037) and a trend toward prolonged procedure time (P = .094). Neck/upper thoracic emphysema and free abdominal air were noted in 31.5% and 35.7%, respectively (95.3% drained), but without relevant sequelae. CONCLUSIONS: POEM has a low rate of SAEs; minor AEs are more frequent but lack a consistent definition. Therefore, based on our experience and literature analysis, we suggest a classification of AEs for POEM. (Clinical trials registration number: NCT01405417.).

Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2†years.

BACKGROUND: The recently developed technique for peroral endoscopic myotomy (POEM) has been shown to be effective in several short-term studies. Longer term outcome data are largely non-existent. OBJECTIVE: To systematically report clinical outcome with a minimum post-POEM follow-up of 2 years. DESIGN: All patients treated consecutively by POEM for achalasia at three centres were retrospectively analysed, with a minimum follow-up of 2 years. The main outcome was the rate of POEM failures (Eckardt score >3) related to follow-up time. RESULTS: Of 85 patients treated, five (5.9%) cases were excluded due to protocol violation or loss to follow-up; the remaining 80 patients (mean age 44.9 years, 54% men) were followed clinically for 29 months (range 24-41). Initial clinical response was observed in 77 cases (96.3%). Clinical recurrences (later failures) were seen in a further 14 cases (17.7%), accounting for a total failure rate of 21.5%. In a multivariate analysis, age and endoscopic reflux signs were independent predictors of treatment success. Of the 17 failures, eight were among the first 10 cases treated in the participating centres. Reflux-associated sequelae included one case of a severe reflux-associated stricture requiring dilatation, and two patients with minor transient Eckardt score elevations curable by proton pump inhibitor (PPI) treatment. Endoscopic signs of reflux oesophagitis, mostly Los Angeles grade A/B, were seen in 37.5% (37/72) at the 2-year control. CONCLUSIONS: In this multicentre retrospective analysis, a high initial success rate of POEM is followed by a mid-term recurrence rate of 18%. Reflux oesophagitis, albeit mild, is frequent and should probably be treated by regular low-dose PPI therapy. TRIAL REGISTRATION NUMBER: NCT 01405417 (UKE study).

Complete Antegrade Transapical Deployment of a Branched Aortic Arch Endograft: A Porcine Feasibility Study.

PURPOSE: To describe and prove the concept of a technique for complete transapical deployment of a single-branch aortic arch endograft in a porcine model. METHODS: Eight domestic pigs underwent antegrade transapical delivery of a single-branch arch endograft, including a mating stent-graft to the innominate artery. Technical feasibility, operating time, radiation parameters, and hemodynamic changes were studied according to a standardized protocol during baseline (T0), after establishing the transapical access and through-and-through wire (T1), and after stent-graft deployment (T2). Myocardial and cerebral blood flow status was assessed using fluorescent microspheres (FM) and transit-time flow measurement (TTFM) monitoring. RESULTS: Transapical access, introduction and deployment of the endograft, side branch catheterization, and deployment of the mating stent-graft were feasible in 6 of 8 animals. One animal died due to irreversible heart rhythm disorders and one due to accidental graft rotation during deployment, resulting in unintended coverage of the innominate artery. The mean operating and fluoroscopy times were 223±11 minutes and 27.2±6.3 minutes, respectively. During introduction and deployment of the stent-graft, transient aortic valve insufficiency occurred in all animals. Hemodynamic stability recovered within 10 minutes after retrieval of the delivery system in all animals. The innominate artery was patent, with unchanged TTFM measurements throughout the procedure. FM evaluation revealed stable cerebral blood flow. CONCLUSION: An antegrade transapical access to the aortic arch for implantation of a single-branch endograft is feasible in a porcine model with reversible impact on hemodynamic measures during deployment. Transapical access allows deployment of a complex endograft through a single large-bore access site in a porcine model.

Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study.

Pilot studies have indicated that peroral endoscopic myotomy (POEM) might be a safe and effective treatment for achalasia. We performed a prospective, international, multicenter study to determine the outcomes of 70 patients who underwent POEM at 5 centers in Europe and North America. Three months after POEM, 97% of patients were in symptom remission (95% confidence interval, 89%-99%); symptom scores were reduced from 7 to 1 (P < .001) and lower esophageal sphincter pressures were reduced from 28 to 9 mm Hg (P < .001). The percentage of patients in symptom remission at 6 and 12 months was 89% and 82%, respectively. POEM was found to be an effective treatment for achalasia after a mean follow-up period of 10 months.

Bispectral index guided titration of sevoflurane in on-pump cardiac surgery reduces plasma sevoflurane concentration and vasopressor requirements: a prospective, controlled, sequential two-arm clinical study.

BACKGROUND: Electroencephalographic-based monitoring systems such as the bispectral index (BIS) may reduce anaesthetic overdose rates. OBJECTIVE: We hypothesised that goal-directed sevoflurane administration (guided by BIS monitoring) could reduce the sevoflurane plasma concentration (SPC) and intraoperative vasopressor doses during on-pump cardiac surgery. DESIGN: A prospective, controlled, sequential two-arm clinical study. SETTING: German university medical centre with more than 2500 cardiac surgery interventions per year. PATIENTS: Sixty elective on-pump cardiac surgery patients. INTERVENTION: In group Sevo1.8% (n = 29), the sedation depth was maintained with a sustained inspired concentration of sevoflurane 1.8% before and during cardiopulmonary bypass (CPB). In group SevoBIS (n = 31), the inspired sevoflurane concentration was titrated to maintain a BIS target between 40 and 60. OUTCOME MEASURES: SPC during CPB and the intraoperative administration of noradrenaline. Additional analyses were performed on intraoperative awareness, postoperative blood lactate concentration, duration of mechanical ventilation, intensive care unit length of stay and kidney injury. RESULTS: Mean inspired sevoflurane concentration was 0.8% in group SevoBIS, representing a 57.1% reduction (P < 0.001) compared with group Sevo1.8%. The mean SPC was 42.3 µg ml(-1) [95% confidence interval (CI) 40.0 to 44.6] in group Sevo1.8% and 21.0 µg ml(-1) (95% CI 18.8 to 23.3) in group SevoBIS, representing a 50.2% reduction (P < 0.001). During CPB, the mean cumulative dose of noradrenaline administered was 13.48 µg kg(-1) (95% CI 10.52 to 17.19) in group Sevo1.8% and 4.06 µg kg(-1) (95% CI 2.67 to 5.97) in group SevoBIS (P < 0.001). Pearson's correlation coefficient (between the cumulative applied dosage of sevoflurane calculated from the area under the curve of the SPC over time and the administered cumulative noradrenaline dose) was 0.607 (P < 0.001). No intraoperative awareness signs were detected. CONCLUSION: BIS-guided titration of sevoflurane reduces the SPC and decreases noradrenaline administration compared with routine care during on-pump cardiac surgery.

Laparoscopic Heller myotomy versus endoscopic balloon dilatation for the treatment of achalasia: a network meta-analysis.

OBJECTIVE: Comparison of short- and long-term effects after laparoscopic Heller myotomy (LHM) and endoscopic balloon dilation (EBD) considering the need for retreatment. BACKGROUND: Previously published studies have indicated that LHM is the most effective treatment for Achalasia. In contrast to that a recent randomized trial found EBD equivalent to LHM 2 years after initial treatment. METHODS: A search in Medline, PubMed, and Cochrane Central Register of Controlled Trials was conducted for prospective studies on interventional achalasia therapy with predefined exclusion criteria. Data on success rates after the initial and repeated treatment were extracted. An adjusted network meta-analysis and meta-regression analysis was used, combined with a head-to-head comparison, for follow-up at 12, 24, and 60 months. RESULTS: Sixteen studies including results of 590 LHM and EBD patients were identified. Odds ratio (OR) was 2.20 at 12 months (95% confidence interval: 1.18-4.09; P = 0.01); 5.06 at 24 months (2.61-9.80; P < 0.00001) and 29.83 at 60 months (3.96-224.68; P = 0.001). LHM was also significantly superior for all time points when therapy included re-treatments [OR = 4.83 (1.87-12.50), 19.61 (5.34-71.95), and 17.90 (2.17-147.98); P ≤ 0.01 for all comparisons) Complication rates were not significantly different. Meta-regression analysis showed that amount of dilations had a significant impact on treatment effects (P = 0.009). Every dilation (up to 3) improved treatment effect by 11.9% (2.8%-21.8%). CONCLUSIONS: In this network meta-analysis, LHM demonstrated superior short- and long-term efficacy and should be considered first-line treatment of esophageal achalasia.

Predictors and outcomes after transcatheter aortic valve implantation using different approaches according to the valve academic research consortium definitions.

OBJECTIVES: We report the results of a large single-center study evaluating predictors and outcomes after transcatheter aortic valve implantation (TAVI) with different devices and access routes according to the Valve Academic Research Consortium (VARC). BACKGROUND: The widespread adoption of TAVI warrants a systematic analysis of outcomes. Only few comprehensive data exist comparing different approaches as selected by a heart team. METHODS: TAVI was performed in 326 consecutive patients (mean age 80.6 ± 7.1 years, 55.5% female) at high risk for surgery with balloon-expandable and self-expanding devices through transfemoral or transapical access. Data were analyzed according to VARC endpoints; predictors of mortality were identified. RESULTS: All-cause mortality was 10.1% (30 days) and 29.9% (1 year) overall and comparable with regard to valve or access choice (P = 0.295) despite different risk profiles at baseline. Device success and 30-day safety endpoints were achieved in 87.1 and 21.2%. Myocardial infarction [hazard ratio (HR) 6.52], stage-2 and -3 acute kidney injury (HR 2.52 and 6.80) and major access site complications (HR 1.96) were independent predictors of 1-year all-cause mortality. Device success had a protective effect (HR 0.58). Baseline predictors included body mass index <20 kg/m(2) (HR 3.20), NYHA class IV (HR 1.87), left ventricular ejection-fraction <30% (HR 2.30), higher STS-PROM scores (HR 1.05 per percent), and age (group 75-85 years, HR 0.47). CONCLUSIONS: Comparable results were achieved with different devices and access routes in a heart team approach. Baseline and perioperative predictors of all-cause mortality were identified, contributing to the refinement of patient and device selection criteria for TAVI.

Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: A prospective multicenter observational study.

OBJECTIVE: Early identification of patients at risk of space-occupying "malignant" middle cerebral artery (MCA) infarction (MMI) is needed to enable timely decision for potentially life-saving treatment such as decompressive hemicraniectomy. We tested the hypothesis that acute stroke magnetic resonance imaging (MRI) predicts MMI within 6 hours of stroke onset. METHODS: In a prospective, multicenter, observational cohort study patients with acute ischemic stroke and MCA main stem occlusion were studied by MRI including diffusion-weighted imaging (DWI), perfusion imaging (PI), and MR-angiography within 6 hours of symptom onset. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. RESULTS: Of 140 patients included, 27 (19.3%) developed MMI. The following parameters were identified as independent predictors of MMI: larger acute DWI lesion volume (per 1 ml odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06; p < 0.001), combined MCA + internal carotid artery occlusion (5.38, 1.55-18.68; p = 0.008), and severity of neurological deficit on admission assessed by the National Institutes of Health Stroke Scale score (per 1 point 1.16, 1.00-1.35; p = 0.053). The prespecified threshold of a DWI lesion volume >82 ml predicted MMI with high specificity (0.98, 95% CI 0.94-1.00), negative predictive value (0.90, 0.83-0.94), and positive predictive value (0.88, 0.62-0.98), but sensitivity was low (0.52, 0.32-0.71). INTERPRETATION: Stroke MRI on admission predicts malignant course in severe MCA stroke with high positive and negative predictive value and may help in guiding treatment decisions, such as decompressive surgery. In a subset of patients with small initial DWI lesion volumes, repeated diagnostic tests are required.

Carbonic anhydrase IX in tumor tissue and sera of patients with primary cervical cancer.

BACKGROUND: Carbonic anhydrase IX (CAIX) is a membranous expressed metalloenzyme involved in pH homeostasis and cell adhesion. The protein is overexpressed in a variety of tumors and potentially associated with negative outcome. This study was designed to investigate the prognostic role of CAIX in serum and tumor tissue of patients with primary cervical cancer. METHODS: Tumor samples of 221 consecutive patients with primary cervical cancer who underwent surgery between 1993 and 2008 were analyzed for CAIX expression by immunohistochemistry. Additionally, preoperative serum CAIX concentrations were determined by ELISA in a subset of patients. Correlation with intratumoral CAIX expression as well as clinicopathological factors and outcome was analyzed. RESULTS: CAIX expression was observed in 81.9% of the tumor specimens; 62.0% showed a moderate or strong staining intensity. Moderate/strong expression was associated with squamous histology (p=0.024), advanced tumor stage (p=0.001), greater invasion depth (p=0.025), undifferentiated tumor grade (p<0.001) and high preoperative SCC-Ag values (p=0.042). Furthermore patients with moderate/strong intratumoral CAIX expression had a higher number of metastatic lymph nodes compared to those with none/weak intratumoral expression levels (p=0.047) and there was a non-significant association between high intratumoral CAIX expression and shorter survival (p=0.118). Preoperative serum concentrations of CAIX ranged between 23 and 499 pg/mL and did not correlate with intratumoral expression or other clinicopathological variables. CONCLUSION: CAIX is associated with advanced tumor stages and lymph node metastases in cervical cancer, potentially representing a new target in this disease. In contrast to other epithelial cancers we could not observe a correlation between serum CAIX and its intratumoral expression.

Relationship between ambient temperature and severe acute poisoning by alcohol and drugs.

AIM: To test the hypothesis that severe acute poisoning by alcohol and drugs is more frequent at higher rather than at lower ambient temperatures. METHOD: This was a prospective observational study performed in a prehospital setting under marine west coast climate conditions. Data from the Emergency Medical Service in Hamburg (Germany) and data from the local weather station were evaluated over a 5-year period. Temperature data were obtained and matched with the associated rescue mission data, which were divided into the following groups: 1) alcohol poisoning, 2) opioid poisoning, 3) poisoning by sedatives/hypnotics, multiple drugs, volatile solvents, and other psychoactive substances. Lowess-Regression analysis was performed to assess the relationship between ambient temperature and frequency of severe acute poisoning. Additionally, three temperature ranges were defined in order to compare them with each other with regard to frequency of severe poisoning (<10 °C vs. 10-20 °C vs. >20 °C). The severity of emergencies was assessed using the National Advisory Committee for Aeronautics (NACA) scoring system. RESULTS: In 1535 patients, severe acute alcohol or drug poisoning associated with loss of consciousness, hypotension, and impaired respiratory function was treated (alcohol: n = 604; opioids: n = 295; sedatives/hypnotics/multiple drugs: n = 636). Compared to mild temperatures (10-20 °C), the frequency of poisoning increased in all three groups at higher temperatures and decreased at lower temperatures (p < 0.01). No significant correlation was found between severity of emergencies and temperature. CONCLUSIONS: Our results suggest a continuously increasing probability of occurrence of severe acute poisoning by alcohol and drugs with rising temperature.

Sphenoid Bone Pneumatisation on Lateral Cephalograms of Patients With Neurofibromatosis Type 1.

BACKGROUND/AIM: Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease that causes tumors and many developmental disorders, e.g., cranial dysplasia. The purpose of this retrospective study was to analyse the pneumatisation of the sphenoid bone in NF1. PATIENTS AND METHODS: The anonymised lateral cephalograms of 166 NF1 patients and 166 age- and sex-matched controls were examined for anterior-posterior sphenoid pneumatisation. The patient group analysis considered whether the patients had been affected by a facial plexiform neurofibroma (FPNF). RESULTS: Sphenoid pneumatisation was significantly lower in NF1 patients than in controls [odds ratio (OR)=0.184; 95%CI=0.11-0.32; p<0.001]. A FPNF statistically significantly reduced sinus formation in patients (OR=0.38; p=0.002). CONCLUSION: The condition 'NF1' has an effect on sphenoid pneumatisation. The findings are relevant for planning surgical procedures in this region and confirm current concepts to evaluate NF1 as a histogenesis control gene. The examination technique and basis of calculation presented here are easy-to-use and low-irradiation exposure instruments for screening for differences in sphenoid bone pneumatisation in defined populations.

Supernumerary teeth of permanent dentition in patients with neurofibromatosis type 1.

PURPOSE: The purpose of the study was the investigation of supernumerary teeth (ST) in the permanent dentition of patients with neurofibromatosis type 1 (NF1). MATERIAL AND METHODS: The panoramic radiographs of 200 NF1 patients were analysed for ST. The potential impact of certain neurogenic facial tumours on the measured variable was investigated separately. The results were compared to dental findings in panoramic radiographs of 200 age- and sex-matched controls. RESULTS: The total number of ST in all individuals was 23 in 12 patients (3% of total population). However, all ST had developed in the group of NF1 patients (6%), (p = 0.0004). ST were particularly common distal to the molar region. Although ST occur in the region of facial plexiform neurofibroma, the numerical aberrations of the dentition are independent of specific type of facial nerve sheath tumour. CONCLUSION: The unusual accumulation of ST in the terminal sections of molar development could be an indicator of preferred points of developmental disorder, in which the genetic predisposition of the patient is involved. Reviewing the results of other NF1 patient collectives is desirable.

Influence of age, sex and hospitalisation on the administration of tuberculosis medication: an evaluation of routine data from a German health insurer.

BACKGROUND: So far, there is no reliable information on the drugs actually taken by tuberculosis patients. With billing data from a large German health insurance company, valid data from practice will be used for analysis. The objective here is to use the claims data of a health insurer to gain an insight into the prescriptions issued to patients with tuberculosis in Germany. METHODS: The study design encompasses a longitudinal, analytical observational study of selected insurance holders. Descriptive analyses of the outpatient drug supply of pulmonary tuberculosis patients are determined for 6 payroll years. We have studied whether different doses of tuberculosis medication are associated with age, sex, inpatient status and comorbidity. Quantile regression is used as a method to identify subgroups or characteristic dosages. RESULTS: The number of defined daily doses prescribed per patient varies among insurance holders and encompasses widely differing timeframes. Higher doses are observed with increasing age, as well as in patients with tuberculosis-related hospitalisations. The sex of the patient has no identifiable effect on the prescribed doses for any of the first-line tuberculosis drugs. Comorbidity partially has a significant impact on the duration and intensity of tuberculosis drug prescriptions.

Effect of an interactive cardiopulmonary resuscitation assist device with an automated external defibrillator synchronised with a ventilator on the CPR performance of emergency medical service staff: a randomised simulation study.

BACKGROUND: The present study evaluates whether the quality of advanced cardiac life support (ALS) is improved with an interactive prototype assist device. This device consists of an automated external defibrillator linked to a ventilator and provides synchronised visual and acoustic instructions for guidance through the ALS algorithm and assistance for face-mask ventilations. METHODS: We compared the cardiopulmonary resuscitation (CPR) quality of emergency medical system (EMS) staff members using the study device or standard equipment in a mannequin simulation study with a prospective, controlled, randomised cross-over study design. Main outcome was the effect of the study device compared to the standard equipment and the effect of the number of prior ALS trainings of the EMS staff on the CPR quality. Data were analysed using analyses of covariance (ANCOVA) and binary logistic regression, accounting for the study design. RESULTS: In 106 simulations of 56 two-person rescuer teams, the mean hands-off time was 24.5% with study equipment and 23.5% with standard equipment (Difference 1.0% (95% CI: -0.4 to 2.5%); p = 0.156). With both types of equipment, the hands-off time decreased with an increasing cumulative number of previous CPR trainings (p = 0.042). The study equipment reduced the mean time until administration of adrenaline (epinephrine) by 23 s (p = 0.003) and that of amiodarone by 17 s (p = 0.016). It also increased the mean number of changes in the person doing chest compressions (0.6 per simulation; p < 0.001) and decreased the mean number of chest compressions (2.8 per minute; p = 0.022) and the mean number of ventilations (1.8 per minute; p < 0.001). The chance of administering amiodarone at the appropriate time was higher, with an odds ratio of 4.15, with the use of the study equipment CPR.com compared to the standard equipment (p = 0.004). With an increasing number of prior CPR trainings, the time intervals in the ALS algorithm until the defibrillations decreased with standard equipment but increased with the study device. CONCLUSIONS: EMS staff with limited training in CPR profit from guidance through the ALS algorithm by the study device. However, the study device somehow reduced the ALS quality of well-trained rescuers and thus can only be recommended for ALS provider with limited experience.

Relationship between ambient temperature and frequency and severity of cardiovascular emergencies: A prospective observational study based on out-of-hospital care data.

OBJECTIVE: To test the hypothesis that more cardiovascular emergencies occur at low rather than at high temperatures under moderate climatic conditions. METHODS: This was a prospective observational study performed in a prehospital setting. Data from the Emergency Medical Service in Hamburg (Germany) and from the local weather station were evaluated over a 5-year period. Temperature data were matched with the associated rescue mission data. Lowess-Regression analysis was performed to assess the relationship between the temperature and the frequency of individual cardiovascular emergencies. In addition, three threshold-temperatures (0°C, 10°C, 20°C) were defined in order to determine the frequency of cardiovascular emergencies above and below each cut-off value. The severity of emergencies was assessed using the National Advisory Committee for Aeronautics (NACA) scoring system. RESULTS: A total of 35,390 cardiovascular emergencies were treated by Emergency Physicians. Transient Loss of Consciousness increased at high temperatures (above 20°C): +43% (95%-CI: [27%; 59%]). In contrast, Coronary Artery Disease +26% (95%-CI: [17%; 34%]), Cardiac Pulmonary Edema +21% (95%-CI: [14%; 27%]), Hypertensive Urgency +18% (95%-CI: [10%; 25%]) and Cerebrovascular Accident +17% (95%-CI: [8%; 24%]) increased at low temperatures, particularly below 10°C (significance level for all: p<0.001). No temperature-related effect was seen in Cardiac Arrhythmia and Pulmonary Embolism and no significant correlation was found between the severity of emergencies and temperature. CONCLUSIONS: Our findings suggest that some cardiovascular emergencies such as Coronary Artery Disease, Cardiac Pulmonary Edema, Hypertensive Urgency and Cerebrovascular Accident are more frequent in low temperatures even under mild climatic conditions.

Reliability of transcardiopulmonary thermodilution cardiac output measurement in experimental aortic valve insufficiency.

BACKGROUND: Monitoring cardiac output (CO) is important to optimize hemodynamic function in critically ill patients. The prevalence of aortic valve insufficiency (AI) is rising in the aging population. However, reliability of CO monitoring techniques in AI is unknown. The aim of this study was to investigate the impact of AI on accuracy, precision, and trending ability of transcardiopulmonary thermodilution-derived COTCPTD in comparison with pulmonary artery catheter thermodilution COPAC. METHODS: Sixteen anesthetized domestic pigs were subjected to serial simultaneous measurements of COPAC and COTCPTD. In a novel experimental model, AI was induced by retraction of an expanded Dormia basket in the aortic valve annulus. The Dormia basket was delivered via a Judkins catheter guided by substernal epicardial echocardiography. High (HPC), moderate (MPC) and low cardiac preload conditions (LPC) were induced by fluid unloading (20 ml kg-1 blood withdrawal) and loading (subsequent retransfusion of the shed blood and additional infusion of 20 ml kg-1 hydroxyethyl starch). Within each preload condition CO was measured before and after the onset of AI. For statistical analysis, we used a mixed model analysis of variance, Bland-Altman analysis, the percentage error and concordance analysis. RESULTS: Experimental AI had a mean regurgitant volume of 33.6 ± 12.0 ml and regurgitant fraction of 42.9 ± 12.6%. The percentage error between COTCPTD and COPAC during competent valve function and after induction of substantial AI was: HPC 17.7% vs. 20.0%, MPC 20.5% vs. 26.1%, LPC 26.5% vs. 28.1% (pooled data: 22.5% vs. 24.1%). The ability to trend CO-changes induced by fluid loading and unloading did not differ between baseline and AI (concordance rate 95.8% during both conditions). CONCLUSION: Despite substantial AI, transcardiopulmonary thermodilution reliably measured CO under various cardiac preload conditions with a good ability to trend CO changes in a porcine model. COTCPTD and COPAC were interchangeable in substantial AI.

Predictive values derived from lower wisdom teeth developmental stages on orthopantomograms to calculate the chronological age in adolescence and young adults as a prerequisite to obtain age-adjusted informed patient consent prior to elective surgical procedures in young patients with incomplete or mismatched personal data.

Introduction: Surgical procedures require informed patient consent, which is mandatory prior to any procedure. These requirements apply in particular to elective surgical procedures. The communication with the patient about the procedure has to be comprehensive and based on mutual understanding. Furthermore, the informed consent has to take into account whether a patient is of legal age. As a result of large-scale migration, there are eventually patients planned for medical procedures, whose chronological age can't be assessed reliably by physical inspection alone. Age determination based on assessing wisdom tooth development stages can be used to help determining whether individuals involved in medical procedures are of legal age, i.e., responsible and accountable. At present, the assessment of wisdom tooth developmental stages barely allows a crude estimate of an individual's age. This study explores possibilities for more precise predictions of the age of individuals with emphasis on the legal age threshold of 18 years. Material and Methods: 1,900 dental orthopantomograms (female 938, male 962, age: 15-24 years), taken between the years 2000 and 2013 for diagnosis and treatment of diseases of the jaws, were evaluated. 1,895 orthopantomograms (female 935, male 960) of 1,804 patients (female 872, male 932) met the inclusion criteria. The archives of the Department of Diagnostic Radiology in Dentistry, University Medical Center Hamburg-Eppendorf, and of an oral and maxillofacial office in Rostock, Germany, were used to collect a sufficient number of radiographs. An effort was made to achieve almost equal distribution of age categories in this study group; 'age' was given on a particular day. The radiological criteria of lower third molar investigation were: presence and extension of periodontal space, alveolar bone loss, emergence of tooth, and stage of tooth mineralization (according to Demirjian). Univariate and multivariate general linear models were calculated. Using hierarchical multivariate analyses a formula was derived quantifying the development of the four parameters of wisdom tooth over time. This model took repeated measurements of the same persons into account and is only applicable when a person is assessed a second time. The second approach investigates a linear regression model in order to predict the age. In a third approach, a classification and regression tree (CART) was developed to derive cut-off values for the four parameters, resulting in a classification with estimates for sensitivity and specificity. Results: No statistically significant differences were found between parameters related to wisdom tooth localization (right or left side). In univariate analyses being of legal age was associated with consecutive stages of wisdom tooth development, the obliteration of the periodontal space, and tooth emergence, as well with alveolar bone loss; no association was found with tooth mineralization. Multivariate models without repeated measurements revealed imprecise estimates because of the unknown individual-related variability. The precision of these models is thus not very good, although it improves with advancing age. When calculating a CART-analysis and a receiver operating characteristics - area under the curve of 78% was achieved; when maximizing both specificity and sensitivity, a Youden's index of 47% was achieved (with 73% specificity and 74% sensitivity). Discussion: This study provides a basis to help determine whether a person is 18 years or older in individuals who are assumed to be between 15 and 24 years old. From repeated measurements, we found a linear effect of age on the four parameters in the individuals. However, this information can't be used for prognosis, because of the large intra-individual variability. Thus, although the development of the four parameters can be estimated over time, a direct conclusion with regard to age can't be drawn from the parameters without previous biographic information about a person. While a single parameter is of limited value for calculating the target age of 18 years, combining several findings, that can be determined on a standard radiography, may potentially be a more reliable diagnostic tool for estimating the target age in both sexes. However, a high degree of precision can't be achieved. The reason for persistent uncertainty lies in the wide chronological range of wisdom tooth development, which stretches from well below to above the 18th life year. The regression approach thus seems not optimal. Although sensitivity and specificity of the CART-model are moderately high, this model is still not reliable as a diagnostic tool. Our findings could have impact, e.g. on elective surgeries for young individuals with unknown biography. However, these results cannot replace social engagement, in particular thorough physical examination of patients and careful registration of their histories. Further studies on the use of this calculation method in different ethnic groups would be desirable.